Ulcerative Colitis

Abstract

<h3>Abstract</h3> The daily sleep/wakefulness cycle is regulated by coordinated interactions between sleep- and wakefulness-regulating neural circuitry. However, the detailed neural circuitry mediating sleep is far from understood. Here, we found that glutamic acid decarboxylase 67 (Gad67)-positive GABAergic neurons in the ventral tegmental area (VTA_Gad67+) are a key regulator of non-rapid eye movement (NREM) sleep in mice. VTA_Gad67+ neurons project to multiple brain areas implicated in sleep/wakefulness regulation such as the lateral hypothalamus (LH) and dorsal raphe nucleus. Chemogenetic activation of VTA_Gad67+ neurons promoted NREM sleep with higher delta power whereas optogenetic inhibition of these neurons induced prompt arousal from NREM sleep under highly somnolescent conditions, but not during REM sleep. <i>In vivo</i> fiber photometry recordings revealed that VTA_Gad67+ neurons showed the highest population activity in NREM sleep and the lowest activity in REM sleep. Acute brain slice electrophysiology combined with optogenetics revealed that VTA_Gad67+ neurons directly innervate and inhibit wake-promoting orexin/hypocretin neurons in the LH by releasing GABA. Taken together, we reveal that VTA_Gad67+ neurons play a crucial role in the regulation of NREM sleep.